Development of polymeric synthetic biomaterial IP-001 to potentiate asystemic immunotherapy of hepatocellular carcinoma via thermal ablation

开发聚合合成生物材料 IP-001 通过热消融增强肝细胞癌的非全身免疫治疗

• 批准号: 10921633
• 负责人: Siu Kit Lam
• 金额: $ 121.99万
• 依托单位: IMMUNOPHOTONICS, INC.
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-16 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10921633
• 关键词: Development; polymeric; synthetic; biomaterial; IP

Abstract: Immunophotonics is a biotech company developing a synthetic biopolymer, IP-001, to potentiate a systemic immunotherapy via microwave (MWA) thermal tumor ablation for treatment of Hepatocellular carcinoma (HCC). The goal of this SBIR Fast Track is to complete preclinical safety and efficacy testing to support an investigational new drug (IND) application based on the feedback from a meeting with the FDA. Significance: HCC is the fourth most common cause of cancer-related death worldwide, with 42,030 new cases in the U.S. in 2019. This rise is partly due to an increase in hepatitis-induced cirrhosis and non-alcoholic steatohepatitis (NASH) associated with obesity and diabetes. Currently, hepatic transplant and surgical resection provide the best opportunity for long term remission, but less than 20% of patients are eligible. Non- surgical candidates with regional disease only have a 10.8% five-year survival rate. Thermal liver ablative therapies like MWA are a standard of care alternative to surgeries for BCLC stage 0, A and a subset of stage B HCC patients. However, ablation targets only local tumors, and systemic tumoricidal effects on micro-metastasis are rare, leading to recurrence rate of around 70% after two years. Better therapies for HCC are needed. Product: IP-001 is intended for intratumoral injection immediately after thermal ablation (MWA). It acts by 1) localizing tumor antigens liberated by ablation and prolonging their availability to the immune system and 2) activating immune cells such as antigen-presenting cells. This results in a stronger systemic T cell response that can reduce local recurrence, eliminate metastases, and elicit long-term memory. Investigator-driven trials in advanced breast cancer show a favorable toxicity profile and early signs of systemic efficacy, with some complete responders achieving long-term remission. The company has received clinical trial application (CTA) approval in Switzerland to begin a Phase 1/2 clinical trial in melanoma and soft tissue sarcoma. Impact: In HCC patients who receive MWA ablation, IP-001 aims to lower recurrence by 50% in stage 0, A & B patients and prolong progression-free survival by 50% and overall survival in stage B & C patients with regional disease. IP-001 could revolutionize the field of interventional oncology by transforming it into a means of early immunotherapy that is broadly applicable to other solid cancers without disruption to the standard of care. Approach and Specific Aims: In the Phase I, Immunophotonics will generate feasibility data of MWA+ IP-001 in orthotopic rat HCC model H-4-II-E (in collaboration with Dr. Rob Martin at the University of Louisville) to 1) establish efficacy and generate data demonstrating heightened systemic immune stimulation against cancer, 2) explore potential synergism with systemic immunotherapy, i.e. checkpoint inhibitor anti-PD-1 in mouse HCC model Hepa1-6. In the Phase II segment, Immunophotonics will further determine 1) maximum tolerated dose of IP-001 for liver injection, 2) impacts of common comorbidity NASH/cirrhosis on treatment efficacy, and 3) will develop CMC methods for scaling up and analysis of the drug product.

摘要：Immunophotonics 是一家生物技术公司，开发了一种合成生物聚合物 IP-001，以增强 通过微波 (MWA) 热肿瘤消融进行全身免疫疗法治疗肝细胞癌 癌（HCC）。 SBIR 快速通道的目标是完成临床前安全性和有效性测试，以 根据与 FDA 会议的反馈支持研究性新药 (IND) 申请。 意义：HCC 是全球第四大癌症相关死亡原因，新增 42,030 例 HCC 2019 年美国病例数增加。这一上升的部分原因是肝炎引起的肝硬化和非酒精性肝病的增加 脂肪性肝炎（NASH）与肥胖和糖尿病有关。目前，肝移植和外科手术 切除提供了长期缓解的最佳机会，但只有不到 20% 的患者符合条件。非- 患有局部疾病的手术候选者的五年生存率仅为 10.8%。热肝消融术 MWA 等疗法是 BCLC 0 期、A 期和 B 期子集手术的标准护理替代方案 肝癌患者。然而，消融仅针对局部肿瘤，而对微转移具有全身杀瘤作用 罕见，两年后复发率约为70%。需要更好的 HCC 治疗方法。 产品：IP-001 用于热消融 (MWA) 后立即进行瘤内注射。它的作用是 1) 定位通过消融释放的肿瘤抗原并延长其对免疫系统的可用性2) 激活免疫细胞，例如抗原呈递细胞。这会导致更强的全身 T 细胞反应 可以减少局部复发、消除转移并激发长期记忆。研究者驱动的试验 在晚期乳腺癌中显示出良好的毒性特征和全身疗效的早期迹象，其中一些 完全缓解者实现长期缓解。公司已收到临床试验申请（CTA） 瑞士批准开始黑色素瘤和软组织肉瘤的 1/2 期临床试验。 影响：在接受 MWA 消融的 HCC 患者中，IP-001 旨在将 0、A 和 B 期复发率降低 50% 患者的无进展生存期延长 50%，B 期和 C 期区域性患者的总生存期延长 疾病。 IP-001 可能会彻底改变介入肿瘤学领域，将其转变为早期治疗的手段 免疫疗法广泛适用于其他实体癌症，且不会影响护理标准。 方法和具体目标：在第一阶段，Immunophotonics 将生成 MWA+ IP-001 的可行性数据 原位大鼠 HCC 模型 H-4-II-E（与路易斯维尔大学的 Rob Martin 博士合作）至 1) 建立功效并生成数据，证明增强的全身免疫刺激对癌症的作用， 2) 探索与全身免疫疗法（即检查点抑制剂抗 PD-1）在小鼠 HCC 中的潜在协同作用 型号 Hepa1-6。在II期阶段，Immunophotonics将进一步确定1）最大耐受剂量 用于肝脏注射的 IP-001，2) 常见合并症 NASH/肝硬化对治疗效果的影响，以及 3) 将开发用于扩大和分析药品的 CMC 方法。